The response of the kidneys to changes in acid-base balance includes both immediate changes in the activity and/or number of transporters in the membrane and longer-term changes in the synthesis of transporters. For example, with metabolic acidosis, H+ secretion is stimulated by multiple mechanisms, depending on the particular nephron segment. First, the decrease in intracellular pH that occurs with acidosis will create a more favorable cell-to–tubular fluid H+ gradient and thereby make secretion of H+ across the apical membrane more energetically favorable. Second, the decrease in pH may lead to allosteric changes in transport proteins, thereby altering their kinetics. Lastly, transporters may be shuttled to the membrane from intracellular vesicles. With long-term acidosis the abundance of transporters increases, either by increased transcription of appropriate transporter genes or by increased translation of transporter mRNA.
eA third group of intercalated cells shares features of both H+-secreting and HCO3 −-secreting intercalated cells. The precise function of this cell type in acid-base transport is not fully understood. fTraditionally it was believed that intercalated cells were only involved in acid-base transport. There is now good evidence that NaCl reabsorption is also carried out by intercalated cells (B type). Reabsorption of NaCl occurs by the tandem operation of an apical membrane Cl−/HCO3 − anti-porter (pendrin) and an apical membrane Na+/HCO3 −/2Cl− antiporter (NDCBE). This mechanism of NaCl reabsorption is inhibited by thiazide diuretics.
•Fig. 37.4 CellularmechanismsforreabsorptionandsecretionofHCO3− byintercalatedcellsofthedistaltubuleandcollectingduct.OnlytheprimaryH+ andHCO3− transportersareshown.ATP,adenosinetriphosphate;CA,carbonicanhydrase.
•Fig. 37.5 ExamplesofcellularH+ andHCO3− sensors.ATP,adenosinetriphosphate;cAMP,cyclicadenosinemonophosphate;GPCR,Gprotein–coupledreceptor;IRR,insulinreceptor–relatedreceptor;Pyk2,nonreceptortyrosinekinase;sAC,solubleadenylylcyclase.(Adaptedfrom:LevinLR,BuckJ.Annu Rev Physiol 2015;77:347.)